Book reviews

Prion diseases constitute a class of transmissible spongiform encephalopathies (TSEs) that correspond to fatal neurodegenerative disorders in both humans and animals and are manifested as infectious, genetic and sporadic diseases. A well-known candidate in this class is the mad cow disease or bovine spongiform encephalopathy that is infectious to humans. The human version of mad cow is known as Creutzfeldt–Jakob disease (CJD) that was first reported in the 1920s. The other widely characterized disease is scrapie in sheep and was initially reported in the 18th century in Europe. A common mechanistic thread has now been established between mad cow, scrapie and other TSEs in animals and CJD, kuru, fatal familial insomnia and Gerstmann–Sträussler–Scheinker syndrome in humans. A historical account on the TSEs reveals that in order to describe the unusual biological properties of the scrapie agent, the ‘slow virus’ hypothesis was just beginning to be accepted during the 1960s and 1970s. Stanley Prusiner serendipitously entered into the field in the 1970s, broke the status quo, revolutionized the understanding, solved the mystery and created an entirely new paradigm that challenged the tenets of modern biology. The identification and elucidation of molecular details of the causative (scrapie) agent of TSEs by Prusiner represent a fascinating saga in modern biomedical science that has been chronicled by him in this book. This book is a first-person account providing a fascinating description of the development of the prion story that represents a disruptive and discontinuous quantum leap in modern biology. It starts with a preface, introduction and a brief narration of his childhood days. The chapter on ‘The beginning of an odyssey’ describes how he came upon the research problem in 1972 during his residency at UCSF, USA. One day, the hospital page operator summoned him to say that he was assigned a patient for evaluation of a rapidly progressive dementia, which was later diagnosed as CJD. This fortuitous call would later change his scientific career for the few decades to follow and would revolutionize the biological paradigm. He beautifully describes his harrowing journey through the scrapie field which was at that time populated with a torrent of conjectures concerning the composition of the scrapie form exhibiting unusual radiation resistance. In the midst of many plausible structural hypotheses, Prusiner decided to purify the scrapie agent and identify its molecular composition using an array of diligent and elegant approaches akin to chemists’ approach that turned out to be a daunting task. He then recollects how his journey was impeded by an undisciplined approach from a different laboratory that claimed to have discovered DNA viroid as the infectious agent. Also, he had to wait for nearly three years to visit New Guinea and examine the kuru patients, which was absolutely critical for his investigation at that time. The narration of the surrounding events, academic politics behind him and many interesting scientific characters and peers, both supportive and unsupportive, during the entire course of his investigation is simply astonishing. He rightly says, ‘there were times when little but my naïveté and exuberance sustained me’. He then describes his fascinating journey that led to the discovery of the novel protein and states as to how an astounding amyloid story unravelled in his laboratory. His tedious, painstaking and meticulous experiments that spanned two decades ruled out the slow viruses hypothesis and revealed that the disease causing scrapie agent is an aberrant (misfolded) form of an endogenous protein, which he termed as the prion protein, devoid of any genetic material such as nucleic acids. Naming the protein as the prion protein is a quite interesting story in itself. He constructed a two-dimensional matrix with ‘i-n-f-e-c-t-i-o-u-s’ along the X-axis and ‘p-r-o-t-e-i-n’ along the Y-axis and after considering many possibilities he finally came up with ‘prion’, with a pronunciation ‘pree-on’. A line of investigations revealed that the misfolded isoform of the prion protein has an unusual (conformational) replication property by which it recruits the correctly folded native form and stimulates (deadly) conformational switch through aggregation and culminates into ordered amyloid aggregates. This autocatalytic chain reaction converts the (benign) good form (‘Dr Jekyll’) into the (infectious) bad form (‘Mr Hyde’) through binding, misfolding and corrupting events that can account for its infectivity. For this groundbreaking discovery, in 1997, Prusiner was awarded the Nobel Prize for Physiology or Medicine. Similar prionlike mechanism is now believed to underlie a number of debilitating proteinfolding disorders such as Alzheimer’s and Parkinson’s diseases that are characterized by amyloid deposits that ravage and riddle the brain. Interestingly, more recent studies have shown that the prionlike amyloid mechanisms could serve as functional ‘information transfer’ means, for instance long-term memory, in many organisms. This book narrates many interesting stories that depict the genesis of an extraordinary phenomenon in modern biological sciences and the ultimate triumph of an invincible spirit. This memoir captures Prusiner’s extraordinary passion, emotions, drawn-out and strenuous battle for tenure/grants/laboratory space and his perseverance against formidable skepticism and hostile reactions. In his book he rightly says, ‘I feared that neither science historians nor journalists could construct an accurate narrative of my investigations.’ This enthralling book is written for non-specialists with little or no formal background in biology. This book is a must read, not just for specialists, but for every practitioner of science. This story will act as a powerful stimulus to the younger generation of scientists, especially students, postdocs and assistant professors who are willing to take up challenging research problems in their scientific career.

This is a very interesting and important little paper. We could have wished that the engraving had given a better illustration than we found; however the description is, we conceive, quite satisfactory. This we shall transcribe, in order to give the history all the publicity which the author requests, for his own information, and, we add, for the information or minute attention of any other practitioners who may meet with similar cases. <e After exposure to damp and cold, the patients complain of a tickling in the throat, attended with great heat, and the sensation of having been blistered, gradually extending over the palate and Schneiderian membrane, exciting much uneasiness and itching in the nose and all the affected parts. 4g Critical Analysis.
ther it be supposed a disease sui generis, from its resisting all knowrt remedies, or merely a pseudo-syphilitic or mercurial complaint. " It is certain that it has generally occurrcd to those who had ?used mercury for a real or supposed lues; but I have seen three cases where that medicine had never been used, nor any venereal affection even suspected ; one of them was a married woman, who had three healthy children during five years that she suffered under it, and had submitted to every plan of cure that could be devised, by numbers of medical gentlemen to whom she had applied. Like all others in this disease, mercury, in any shape or form, w as to her invariably injurious. " In the only case I have seen prove fatal, the uvula and soft palate sloughed away from time to time. Little aphthous crusts formed on the back part of the fauces, falling off successively, and succeeded by round black ulcers, which gradually penetrated deeper and deeper, destroying great part of the nose and internal ears. She could not swallow solid food in this stage of the complaint, her hair fell off, debility and swelling in various parts supervened, and death at length terminated her sufferings. " In any of the cases I have seen, the constitution exhibited no characteristic mark of a scrofulous diathesis. " I do not think it necessary to enlarge on this subject at present, nor to enumerate what local and constitutional remedies had been tried, but shall probably, in a short time, submit a few cases of it to your readers, in a detailed manner; and, in the mean time, hope that more light may be thrown on this matter by some abler and more experienced practitioner." In conformity with the wishes of the author, we shall offer a few conjectures, and such only they must be considered, as we profess never to have seen similar cases pervade a district in the manner here described.
Though exposure to damp and cold are spoken of as the external causes, we take the liberty to hint that these causes are so general as should make us backward in admitting thein to be sufficient in themselves. Enquire then?have the patients slept in an exposed place, with their mouths open, by which means noxious insects may have attached themselves to the diseased parts as a nidus ?
Has the disease been confined to a certain district, or does it appear that those who are affected have by any means all breathed the air of any particular spot?
Is it probable that the snuff-box of any individual may have been affected, and others by the common courtesy of offering and accepting the box?
Were those who suffered most great snuff-takers; and were any affected who do not use that herb ? 3 It Edinburgh Medical and Surgical Journal. 49 It appears that one woman had three healthy children during her illness: were they subsequently affected by the effluvia from the breath, or in any other way ?
Lastly, is a new morbid poison (certainly not sivvins) convej^ed by the promiscuous use of the same tobacco-pipe? The succession of sloughs is very similar to the nigritts serpens of Celsus, or the sloughing phagedena of some modern writers.
We could wish the engraving had been explained by numerical figures or letters, with references; and should still wish to see the outlines with such references.
We are encouraged to offer these hints by the invitation of Mr. Murray, and, as he is so good as to promise us further information, and more detailed cases, we take the liberty of adding a few more lines.
Only one case, we are told, has proved fatal?Are all the others becoming progressively worse, or are some of them healed spontaneously ?
Are the symptoms uniform in all, excepting as to greater or less degree of quickness in their progress?
Have any cases recovered which were exactly similar to the fatal one in its early stage ?
On the first appearance of the symptoms, would it be desirable to try the effect of a very strong solution of Kali purum as a gargie, and, if necessary, injected up the nose? Art. VI.?Case of Artificial Pupil. By Mr. Moore, Surgeon, Belfast. irrcm what has been written of late years on the subject of artificidT pupil, it appears that different methods have been adopted since the original proposal by Mr. Cheselden, and, according to the abettors of each, with greater or less success.
The object of the operation being simply that of forming an opening through some part of the iris, as a substitute for the one which has become obliterated by inflammation or accident, or rendered useless by a large central opacity of the cornea, it is manifest that the process must be varied according to the nature and character of the cause which occasioned loss of sight. Hence, under particular circumstances, one mode will be found preferable to another. Sut, in ail, that operation is the most eligible, which, whilst accomplished with least pain and injury to other parts of the Urgan, leaves the whole in a condition the nearest approaching to its natural state. Every deviation from these particulars must render the eye less sightly and less useful.
From these considerations, and for the reasons stated by Mr. Myore, viz. that " when he has seen it performed, there No,'20i).
h v was 50 Critical Analysis.
was a considerable degree of inflammation, and the cure was very tedious," we bave always regarded the operation proposed by Sir William Adams as by no means unobjectionable.
For, by the method'of proceeding which he recommends, not only is great violence done to the organ of vision, and the opening through the iris left of an immoderate size, but we apprehend the danger of subsequent inflammation must also be great, and the absorption of the disorganized lens proportionably slow. By the entire removal of the crystalline, too, even when transparent, the necessity of ever afterwards using convex spectacles becomes indispensable. The ?lan suggested by our author, if generally practicable, certainly offers several important advantages. He describes it in the following words : " Having fixed the eye with a speculum, I pierced the cornea with the extracting knife, half a line from the sclerotica on the outside, and a little above the transverse diameter of the cornea, and continued the incision to its lower part, keeping at the same distance from the sclerotica.
I then introduced a very small hook, and fixed it in the centre of the iris, carefully avoiding the lens* the iris being gently raised, the point of a fine pair of scissors was introduced behind the hook, and the raised part snipped off and brought out. There was a slight effusion of blood from the iris, which rendered the eye turbid. The antiphlogistic plan was continued, as above mentioned, and in about a week the effusion was absorbed, and the eye became clear. We then found the pupil in its proper place, and fully the natural size; such as it usually is in a moderate light, and quite circular, except the part near the external angle, towards which it was lengthened a very little, and the margin of that part not so smooth or well defined as the other part of the circumference. He could now discern colours, point out the different objects in a room; and the panes of a window, or the colour of people's clothes at the opposite side of the street, In a few days he went home to the country with a very useful degree of vision. It is now five months since the operation, and I have lately heard from him. He is able to follow his business aa usual, and the sight of the eye is as good as before the accident, except that the pupil has not the power of contracting, and it is necessary to wear a shade over it in a strong light." By this method of operating, the artificial pupil is made with as little mischief to the eye as by most of the other processes, and the opening corresponds with the situation of the natural pupil, which it more nearly resembles than the inconveniently large transverse pupil formed by the operation to which we have just alluded. The lens, too, remainjng/Cin touched, the cure must be more rapid, and the restored vrsion will approach nearer to its pristine condition. If we' may Edinburgh Medical and Surgical Journal, 51 may be allowed to pass an opinion on its specific merits* it appears to ns to be especially applicable to those instances of obliterated pupil which sometimes occur after the operation of extraction; but that when the pupil has become obliterated by inflammation of the iris, and adhesion of its posterior surface to the capsule of the lens, it cannot be effected in the way proposed by Mr. Moore. Nor, in truth, are we without our suspicion, that even in the case detailed, the lens, by the escape of so large a portion of the vitreous humour actually sunk further back than its usual situation immediately behind the plane of the iris; and that to this circumstance may, perhaps, be ascribed the fact of its having escaped being wounded by the hook or curved scissars.
The operation is, however, well worth recording, and adds to our knowledge in the mode of proceeding with this delicate organ. This appears to have been one of those numerous cases in which active inflammation has gone through all its stages, and the patient has fancied himself well because the immediate urgent symptoms have subsided. The only previous history which could be traced was that, during a severe illness which she had lately gone through, she suffered frequent and long-continued pains in the lower part of the back and belly, extending down the thighs, with a bloody discharge from the rectum and vagina. THE Faculty will be much obliged to Dr. Johnson for supplying a desideratum, which, if we may judge by our own feelings, has long existed. Animals so perpetually in our view, and even in use, the scarcity of which has been for some years so severely felt, claim an interest which it is by no means creditable to have so long overlooked. Many of our brethren are excellent naturalists ; indeed, there are few of the latter description of philosophers who were not originally educated for medicine, which they hive only relinquished on account of the bewitching charms of physics, properly so called. If less attention has of late years been paid to all the more minute structure and habits ot many animals, may we not impute it in part to that illustrious naturalist to whom we are indebted for almost every system now in use.
The arduous task undertaken by Linnaeus of reducing all the objects of nature to classes, orders, genera, species, and varieties, not only excites our astonishment at the boldness of the undertaking, but our gratitude for the manner in which it is executed. But; as no good is unattended with some inconvenience, Dr. Johnson on the Medicinal Leech. 53 convenience, so we cannot help thinking that this habit of systematising has made ns anxious to undertake too much, and too inattentive to the completion of single objects.
Thus we are apt to suppose that it is sufficient to fix on a certain mark lot a genus, and the presence of this with some Other distinction for a species. Having done thus much, our task seems finished ; and the more interesting minutiae of form and habits are either overlooked or passed over as suited to those only who are contented to confine themselves to a few objects in nature. The motto chosen by our author is a very good lesson against this inattention, and we heartily "wish the moderns had followed Aristotle in his designation pf animals whom the moderns are in the habit of calling inferior or more imperfect. In our opinion, less honoured or less attended to, as used by the Stagerite, is a much more becoming expression for the professors of a religion which teaches that Solomon in all his glory was not arrayed like the lillies of the valley, and that not a sparrow falleth to the ground without the same superintendance as governs the af* fairs of men.
" Af? |XtJ %u3tnS>g rv}v TUV UTlfJLUTipuV $bwV 67iiffH?-4siv; ev Tiaai y?p roTa (pv^iy.oTg iveari r? &uv[xagtov.? u Aristotle: B. i. c. 5." The first section contains the medical history of the leech. In this we have an account of the period as high as we can trace its introduction into medicine, which Dr. J. supposes cannot be beyond Themison, the founder of the methodic sect who flourished about the beginning of the Christian a2ra.* From that period, most of the writers by whom the leech is recommended, are named till we approach near enough to the present times. This chapter, like all other collections of historical anecdotes, is more interesting than useful. It, however, makes a necessary part of such a work.
An account of the natural history of the leech follows.
We shall not enter into any controversy concerning generic distinctions, as this would rather become a work devoted exclusively to natural history. It is enough to remark that Dr. Johnson excludes the hirudo complanata and slagnalis from the genus altogether; and, on account of their retractile and tubular tongue, he gives them the appellation Glossipho- then moved in a waving direction, upward and downward. By this action, briskly repeated, the leech is thrown forward, and soon accomplishes its purpose. 44 In winter, leeches resort to deep water; but in summer they delight in the shallows, where they arc more exposed to the influence of the sun. When the weather is very severe in winter, or so dry in summer as to endanger the total drying up of the pools they inhabit, they retire to a considerable depth in the ground, leaving a small aperture to their subterranean habitation. They begin to make their appearance in the water about the latter end of March or the beginning of April. During a bright sunshine they may be seen very actively swimming from place to place; but, should the weather prove cold or cloudy, they confine themselves to the mud. In rainy or windy weather, when the water is agitated, they retire from sight. Just before a thunder-storm, they commonly come up to the surface; and this the leech-gatherers find a good time for collecting them. 44 Leeches are said to predict changes in the weather, with so much accuracy as to serve for barometers. 44 A clergyman residing in France found that a leech, enclosed in a glass vessel half filled with water, and kept in a window of Lis chamber, answered every purpose of a barometer. Each morning, he informs us, the leech had shifted its position, in strict unison with the varying state of the atmosphere. From attentive examination, he was enabled to ascertain,?first, that when the weather was about to be serene and pleasant, the leech remained at the bottom of the vessel without the least movement; secondly, that if it was about to rain, in either the fore or afternoon, it mounted to the surface of the water, and there remained until the return of fine weather; thirdly, that on the approach of boisterous weather, it moved in the water with uncommon swiftness, and never ceased from this motion until the wind began to blow; fourthly, that on the approach of weather attended with thunder and rain, it remained out of the water for several days, appearing agitated and restless; fifthly, that it rested constantly at the bottom of the vessel when a frost was about to commence ; and sixthly, that during the time of srow or rain, it fixed itself at the neck of the vessel, remaining at perfect tast.* Cowper, the celebrated author of The Task, has asserted that leeches, "in point of the earliest intelli. gence, are worth all the barometers in the world.'' Although I cannot agree with our poet, I will not say that leeches are unaffected by the weather, since this is sufficiently proved by their restlessness on its various changes; being affected in like manner with those animals of which the Mantuan bard, in speaking of an approaching shower, gives so natural a description. Georg. lib. i. v. 374. " How far the remarks of either the French clergyman or the poet are worthy of notice, will appear by observing vessels in which leeches are contained. Some leeches will be seen in a state of rest, others in motion ; some at the bottom of the water, others at the surface. I would therefore ask how it is possible they can. furnish any thing like accurate indications of the state of the atmosphere ?" The food of the medicinal leech is said by many writers to consist of worms and larva; of aquatic insects. This our author shows to be erroneous. It might, indeed, be expected from the uniformity of nature, that the same animal is not fed in such different ways. The error, Dr. J. imputes to confounding this with H. Sanguisuga. The following experiments prove, that the H. medicinalis and troctina confine themselves to blood. 41 Having procured a frog, I placed it in a vessel containing half a dozen leeches (II. medicinalis and H. troctina), in which floated a piece of deal. The poor animal, finding itself surrounded, made every effort, but ineffectually, to reach the upper part of the float; while its enemies pursued it with more than common activity. At length one of the leeches settled on the back, and the others affixed themselves to the legs. On the following morning the frog was found dead, presenting, on different parts of its body, no less than eighteen wounds, all bearing the usual triangular appearance." Many other experiments were tried, all tending to the same proofs. Larvae of aquatic insects were also placed in the same vessel, but remained untouched. On the contrary, nothing could exceed the voraciousness of the horse-leech. " Desirous (says Dr. J.) to ascertain how many of the smaller leeches would be swallowed in a given time, I kept two horseleeches in separate vessels for a month, supplying them constantly with the H. vulgaris, both in its dead and living state. " During the whole of this period, I must observe, the water was turbid, notwithstanding its occasional renewal, from the vast dis. engagement of focal matter which floated about, having a thread- not, in two, trace the least vestige of a leech. In the third, I found a leech about half digested, surrounded by a fluid, in colour of a deep brown. The intestine in the others was filled with a similar fluid, but much thicker in point of consistence. " This experiment, with the preceding table, cannot but con. vince us of the activity of the digestive powers in the H. sanguis suga. This indeed may be also determined by a reference to its anatomical structure. In the //. sanguisuga, the intestine is more than double the width of that of the U.medicinalis and H. troctina; and the stomach is not so thickly set with membranous folds or partitions. A difference therefore in regard to food necessarily arises, from this difference of structure.
"To the general law in cold-blooded animals, that digestion proceeds with great slowness,* the experiment just mentioned offers a marked exception." We cannot forbear transcribing the following, to show how little we can depend on those writers who conceive it their duty to explain every thing in natural history. It is much to be regretted that all authors are not careful to dis-? * We learn from that indefatigable experimentalist, Spallanzani, that a lizard, after remaining sixteen days in the stomach of a viper, was found to have lost nothing of its original form?a remarkable instance of the extreme slowness of the digestive powers in cold-blooded animals."?This apparent slow digestion is accounted for by Mr. J. not merely from the deficiency of digestive power in the animal under coJd, but from the absence of any necessity for food. That great physiologist found that food in the stomach of torpid animals underwent no change during the winter.?Edit. tinguish production, were again sub-divided and again re-produced, without the failure of one single instance.'* These experiments I have repeated, but with this wide difference, that I have met with failure in every instance." The author gives a history of his own experiments, which it is not necessary that we should transcribe. It may not be amiss to add the authority of a celebrated, and, I believe, very faithful, naturalist. '? Many, says Miiller, might be easily led into an idea, that an animal whose members, when separated, possess, for a great length of time, their vitality, is capable of re-production; but, he judiciously adds?aliud enim est vitam in singulis partibus aliquamdiu remanere, basque se movere ; aliud in totidem abire animalia: illud pluribus animalium commune est, hoc minus vulgare. In another place this author observes, what is more to the point, that he has endeavoured to ascertain how far this power of re-production in leeches exists; but all his experiments go to prove that leeches have no re-productive power whatever.-j-'' The interest we have felt in this ingenious little performance has induced us to protract our account longer than such an article tnight seem to admit. We shall, therefore, conclude with a summary account of what remains.
The leech is said by some naturalists to be infected with its own particular louse; but Dr. J. has not been able to discover any. Some remarks follow on the mode of propagation, their longevity, vivacious powers, its growth, &c. On these subjects we shall only offer one slight hint to our author, for his further consideration, or our better information. its growth, cannot but be admitted as valid proof of its being long, lived, conformably to the general law, that the longer the time an animal takes in arriving to maturity, the greater is the duration of its life." However general this law may be, we fear, like most others ?which Lord Bacon attempted to establish in physics, it is liable to man}* objections. Most birds arrive early at their fall growth, yet some of them, even in an unnatural state of confinement, are very long-lived.
The third section is 011 the anatomical structure of leeches.
As this is illustrated with very delicate plates, it would be injustice to offer a description without them. We give great credit to the author for the diligence with which he has detected every part he describes. On the disputed subject of the anus, we are ready to join in the surprise he expresses that the justly celebrated j. Hunter should admit, without more minute examination, that the leech is destitute of that part. This may be a very useful hint to those philosophers ^vhose every word is attended to. Mr. Hunter, before he admitted this as fact, ought to have examined for himself, and it is probable that he saw his error before he died, as we find Sir Everard Home using a different language in his Lectures on the Hunterian Musasum. We cannot, however, help expressing a wish that Dr. Johnson, when speaking of the capacity of leeches to resist cold, had referred to Mr.
Hunter's infinitely more philosophical experiments than those which he cites from Bibiena.
We have next a description of the organs of sense, as far as the most diligent research could discover them; and of the mode of breathing, which Dr. J concludes, from very good authority, and his own experiments, is by spiracula.
The internal structure is next minutely traced, and well illustrated by engravings. The hermaphrodite, or rather androgenous character, is well ascertained; and the whole concludes with a chapter on the diseases of this interesting and useful little creature.
To recommend such a performance would be superfluous, as every medical practitioner will find an interest in every part. But, among other uses, we conceive no trifling one to be that, during the dull process of applying leeches, the patient may be entertained with its natural history, and this knowledge being familiar with the younger part of the profession, may instruct as well as induce them to give greater attention to this living charge committed to their care. We have taken this paper out of its order in the volume, because of its connection with the three concluding ones in our Number for May. The subject may be truly called awful, whether we consider the condition of the patient, or the nature of the proposed operation. After a few preliminary remarks, Mr. L. introduces two cases of his own. At the close of the paper he gives a third, and also a fourth, communicated by Dr. P. Latham. u In some bodies (says he) which I have examined after death, appearanr.es have been found analogous to those described by the learned physicians just quoted. The patients died of sulfocalion ; but the progress of the complaint was much slower than in those cases,?the symptoms were not acute, nor did the inspection of the parts disclose any evidences of active inflammation. The mem.
brane covering the chordae vocales was thickened, so as to close the glottis, and a similar thickening extended to a small distance from these parts, accompanied with an cedematous effusion into1 the cellular substance under the membrane. The epiglottis did not partake of the disorder. In one or two instances, this thick, ened state of the membrane was the only change of structure observed ; but in others, it was attended either with ulceration of the Surface near the glottis, appearing as if it had been formed by an abscess which had burst; or with a partial death of one or more of the cartilages of the larynx, viz. the arytenoid, thyroid, or cricoid. The rest of the air passages and the lungs were healthy.
Having, within a short time, performed bronchotomy in two cases of the kind just alluded to, I shall shortly relate the particulars of them." Of these two cases, we shall give the dissection, and some of the author's remarks. The first patient appeared almost in articulo mortis when the operation was performed. He was, however, completely relieved in his respiration, and lived eight days, breathing, without the least difficulty, through the wound, from which there was a copious discharge of thick mucus, and afterwards of purulent fluid. On examination after death,? " The chordce rocales, sacculi laryngis, epiglottis, &c. were perfectly healthy ; their membranous covering, as well as the lining of the trachea, free from every appearance of inflammation; and the rima glottidis of its natural dimensions. There was a small internal 62 Critical Analysis. internal apperture at the back of the larynx, under the glottis, leading into a cavity on the outside of the membrane, which contained about one half of the cricoid cartilage completely bare and loose. This part had previously undergone the change into bone, ?which the cartilages of the larynx, at least the thyroid and cricoid, usually experience before the age of the present patient. " The chest exhibited extensive marks of recent disease, in adhesions of the lungs to the pleuras, and effusion of whey-coloured fluid with flakes of coagulated lymph. The lungs therdselves were also considerably diseased." The second case was not less formidable, when Mr. Lawrence undertook the operation, which was as soon as he was introduced to the patient. Bronchotomy produced a temporary relief; but the passage was soon plugged up by the viscid secretion, and many circumstances prevented a removal of a portion of the trachea. The following is the account of the examination after death : il The membrane of the chordae vocales, sacculi laryngis, and front of the arytenoid cartilages, possessed its natural pale colour, but was thickened and granulated on the surface, so a* completely to\shut the rima glottidis. The affection, entirely confined to the parts just enumerated, occupied a very inconsiderable extent of the membrane, just enough, indeed, to close the entrance of the trachea. The rest of that tube, the epiglottis, and neighbouring parts, and the contents of the chest and abdomen, were perfectly bealthy. A portion of the tube had been cut through longitudinally, at the side of the opening in the trachea, and was nearly detached. " Considering that no part was found diseased in this woman, except a square inch at most of mucous membrane, 1 cannot but ascribe her death to obstructed respiration ; and think it probable the event would have been different, had more complete relief been afforded by the operation." This case introduces another from the Edinburgh Journal, which, to render our remarks at the close of the article more perspicuous, we shall call the 3d case. It was more chronic in its history, having existed, to a certain degree, for several months before the patient applied for relief at the Infirmary. The patient (a female) visited some friends half a mile distant, and returned on foot. The symptoms were so much exasperated that she died on the following day, whilst the operation was under contemplation. , Case the 4th is related by Pelletan in the Clinique Chirurgicale.
... " After an attack of fever, which yielded to the ordinary means, a pain in the throat remained, accompanied with difficulty of swallowing, which increased rapidly, and afterwards with uneasiness in 6$ inbreathing. Nothing unnatural could be observed on looking into the throat. Blisters were applied externally, but the disorder gained ground; and the progress towards suffocation becoming accelerated, Pelletan opened the trachea. It was too late, for the woman died the same day. 1 he membrane of the epiglottis was so much swollen, as. to give that organ a globular figure. The membranous lining of the larynx and pharynx was equally swollen;, and increased in density. The opening of the glottis was reduced to less than one third of its natural size." Many other instances are produced, some of which were under Mr. Lawrence's inspection after death ; but, as he did not witness the early symptoms, we shall not produce them: nor shall we notice his learned references. Though all of them might not be necessary, they are interesting in showing the state of surgery, and the opinions of practitioners at different periods of the world. We only transcribe the following, because we conceive it to be not less valuable lor point than authenticity. It is extracted from the 41(jth number of Phil. Trans.
?4 Critical Analysis, four days, bis breathing being perfectly easy, and his deglutition almost so, we removed the canula, and left the glottis to do its own office.
"The patient was soon perfectly recovered: he breathes, speaks, eats, drinks, and performs all the other offices of life, and goes about his calling as formerly. And now 1 cannot but notice the needless pain some writers arc in about healing up the wound by bandaging, stitching, &c. for we found it easily to fill up of itself in very few days, by on'y dressing it every other day or so with a soft tent made less and less every dressing, and armed, in the common way, with liniment, arcaei." In the subsequent case, related by Mr. Lawrence, he was completely successful; nor can there be a doubt that to his skill and courage the patient is indebted for the preservation of life.
After a few days' hoarseness, 11 on the 7th of July he began to experience a difficulty of breathing, and, to use his wife's expression, to hoop ; that is, to draw his breath with a peculiar sound. The voice was still more .affected, and reduced to a kind of whisper.
He was bled and purged on the 8th. At one in the morning of Wednesday the 12th, he again became much worse; the difficulty of fetching his breath was so great, that his wife said he was like dlately determined on bronchotomy, receiving, in this determination, the sanction of my friends* Mr. Wheeler, the apothecary to the hospital, and Mr. Langstaff, who kindly favoured me with their assistance. I made a perpendicular incision, cut through the cricoid cartilage, and neighbouring part of the trachea, and removed a sufficient portion, of these parts to leave a free opening for respiration. The blistered state of the skin, the depth of the parts in a short and thick neck, the rapid motions of the larynx, and the entrance of blood into the tube from vessels divided in exposing it, produced greater difficulties in the operation than a person would cxpect, who formed his opinion from the ease with which it is accomplished in the dead subject. Two small arteries bled freely: one of them was tied ; but the other could not be secured, on account of its lying completely under the edge of the cricoid, cartilage : it was therefore left, the patient bending forwards that the blood might not flow into the trachea. He breathed quite easily through the artificial opening ; all the agitation and distress ceased ; the skin became cool, and the pulse softer. Soon after he had some sleep, but did not rest much during the night. He took a saline mixture, with small closes of the tartrite of anatomy. The pulse was rapid, and intermittent for two or three days, but he was free from fever.
Breathing was performed entirely through the wound, and the voice, consequently, was completely lost. There was a copious mucous and purulent discharge from the trachea and wound.
On the 21st he was sufficiently recovered to get up. By holding the edges of the wound together, he could breathe through the larynx and speak, but there was still a feeling of difficulty, which made it necessary to open the wound again in has a general debilitating influence in the more chronic forms of the disorder; and that these effects are in themselves fatal, after a certain time, even if the original obstruction be obviated. " 4. That local and general bleeding, blisters, and the various internal means, are usually inefficacious. " 5. That the operation of bronchotomy, by providing an artificial opening for the air, produces complete relief, but, for the reasons mentioned under the third head, it is ineffectual, unless performed very early. <{ 6. That the operation is free from danger, has been many times successfully performed, and has not in any instance produced unpleasant consequences." Some useful observations follow on the mode of conducting the operation.
In a review of the above remarks, it is impossible to ob* ject to the main proposition of an early resort to the operation. But, in another part of the paper, the author proposes that it should precede the usual remedies of bleeding, purging, and blistering. On this we offer at least a fewhints.
The main question to be considered is, Whether the disease is purely inflammatory or not ? That it is in some cases cannot be questioned, because Dr. Roberts cured his patient by early and free blood-letting (see page 413 of our last Number); and we have shown that this practice has been sanctioned by the ablest physicians in all ages. If it has been found insufficient, the operation is not only justifiable but imperiously demanded. But may not cases occur in which the operation should precede every attempt? To this we answer, that in hospital cases we think they often may, because there, it frequently happens that the case may not be seen till it has assumed a chronic form ; that is, till the more urgent symptoms of inflammation have subsided, and the only remaining danger is suffocation from an affection of the larynx, which obstructs the passage of air into the chest, or from such a quantity of secretion as must interrupt the ordinary means of respiration. But in the history of cases in private life, accurately described, the marks of inflammation, ab initio, have usually been sufficient 2 to to authorise the trial of every antiphlogistic means, and even to demand them, before an operation should be attempted on a part, the irritability of which will be greatly increased by the neighbouring inflammation.
On the third proposition we could wish Mr. Lawrence had dwelt longer. We have seen that in acute cynanche the influence on the constitution is sometimes so violent as to induce death, even when the patient has recovered respiration. There is, therefore, reason to believe that in such cases death has been induced by the high action which has been excited, without ending in any of the common effects produced by such cause; that is, without terminating in either adhesion, suppuration, or effusion; for the two patients mentioned by Dr. Baillie breathed freely before death, yet one of them, on a former occasion, had been relieved by free bleeding in the early stage of the disease.
In what may be called the more advanced stage of the dis* ease, the first inquiry should be, whether, in the beginning, high inflammation existed. In all the cases related in this paper, as examined after death, more marks of the sequelae of inflammation were found than are necessary to ascertain its existence. In the first, there was purulent fluid during life ; and the evidence of abscess at the back of the larynx discovered after death. In the second, the same and neighbouring parts, though pale, were thickened with a granulated surface. These are sufficient, in our opinion, to prove a previous violent inflammation, which had probably subsided before the patient arrived at the hospital; and we have no history of the preceding symptoms. In the third case, from the Edinburgh Medical Journal, dissection proved evident marks of early inflammation. It was probably less violent than in some other cases, and, as it terminated in suppuration, the patient was enabled to protract a wretched existence a few months longer. This case was no doubt similar to those mentioned by the learned president in his note transcribed p. 41.5 of our last volume. If the history of the disease does not furnish the symptoms of high inflammation in that part, we must remark again the difficulty of gaining accurate histories from the recollection of the complaints of a servant. The dissection shows phenomena which nothing but inflammation can produce. Pelletan's case, though described as chronic, and though the writer of the paper before us, considers it as a slow affection, commenced with an attack of fever. At this time, probably, high inflammation was excited about the epiglottis and larynx, the parts were thickened, and that thickening not subsiding K 2 sufficiently 68 Critical Analysis.
sufficiently for the necessary action of the parts, induced all the chronic symptoms.
The next case, from the Philosophical Transactions, is peculiarly interesting, not only on account of the success of the practice, but because the author shows how much he was assisted by a reference to those writers who are at present too much undervalued, or too little attended to. 1 hough the writer has not mentioned Celsus, probably because he considered him as a copyist of the Greek physicians, yet it is impossible not to mark the similarity of their observations.
All the parts in view, says Dr. Martin, appeared healthy, only a little drier than ordinary. Celsus's words are, " Internum neque tumor nec rubor ullus apparet sed corpus aridum est, vix spiritus trahitur, membra solvuntur." This he considers the most dangerous form of the disease.
We return now to Mr. Lawrence's successful case. The first symptoms were on the 7th of 1'ebruary, and so considerable, that the patient in breathing was said to hoop, and the voice was reduced to a whisper. On the following day he was bled and purged. The symptoms were somewhat relieved; but on the fourth day afterwards, at one in the morning (the usual period for paroxysms, whether in the beginning or return of acute diseases), the difficulty of breathing was so great that Mr. Parkinson sent his patient